The primary goal of this Career Development Award (K01) is to provide the necessary training and mentoring for Dr. Cruz-Almeida to establish an independent neuroscience research program aimed at studying the neurobiological mechanisms underlying abnormal pain modulation in older adults that may account for increased clinical pain in this population. To meet these career goals the candidate has four specific training objectives in the K01: 1) Develop expertise in advanced neuroimaging techniques and analyses; 2) Increase knowledge about the neurobiology of aging; 3) Develop expertise in cognitive neuroscience; and 4) Enhance translational research skills to function as an independent investigator. These training objectives extend the candidate's previous background in the fields of neuroscience, aging, and pain psychophysics and will be achieved through guided mentorship, didactic experiences, and applied research experiences. The K01 will take place at the University of Florida (UF) College of Medicine under the direct mentorship of Dr. Roger Fillingim, with co-mentorship from Dr. Ronald Cohen, Dr. David Vaillancourt and Dr. Joseph Riley. All mentors are nationally and internationally respected experts in the fields of pain and aging (Drs. Fillingim/Riley), cognitive neuroscience and neuroimaging (Dr. Cohen) and neuroscience and neuroimaging (Dr. Vaillancourt) research. The environment is ideal for this project because the University places a strong emphasis on aging research including pain and aging studies. The necessary laboratories, equipment, and supplies needed to complete the series of studies described in this application are available to the candidate via the Institute on Aging. Recent studies show that older adults exhibit dysfunctional pain modulation characterized by increased facilitation and reduced inhibition of pain, which increases the risk for experiencing clinical pain. However, knowledge of the supraspinal mechanisms contributing to age-related dysfunctional pain modulation is lacking, specifically relating to brain structure and function. Thus, the long-term goal of the candidate's research program is to identify the neurobiological mechanisms contributing to dysfunctional pain modulation of older adults. The candidate will examine the structural (aim 1) and functional (aim 2) connectivity of cortico-striatl regions in older and younger adults and determine their associations with an individual's pain modulatory capacity (aim 3). The proposed research addresses a significant gap in the literature and is the first to evaluate the age-related changes in the neural substrates of endogenous pain modulation. The identification of key top- down modulatory brain networks will increase our understanding of age-related changes in pain processing that may ultimately lead to personalized, targeted therapies. Given the expected increase and burden of chronic pain in older adults in the coming decades, effective strategies to reduce the risk of older adults experiencing chronic pain are urgently needed. Importantly, this study will also provide the neuroimaging training and expertise to propel a promising young investigator at the intersection of pain and aging neuroscience research.